RT Journal Article
T1 Astrocytic Ca2+ activation by chemogenetics mitigates the effect of kainic acid-induced excitotoxicity on the hippocampus
A1 Hernández Martín, Nira
A1 Gómez Martínez, María
A1 Bascuñana, Pablo
A1 Fernández de La Rosa, Rubén
A1 García García, Luis
A1 Gómez Oliver, Francisca
A1 Solas, Maite
A1 Martín, Eduardo Daniel
A1 Pozo García, Miguel Ángel
AB Astrocytes play a multifaceted role regulating brain glucose metabolism, ion homeostasis, neurotransmitters clearance, and water dynamics being essential in supporting synaptic function. Under different pathological conditions such as brain stroke, epilepsy, and neurodegenerative disorders, excitotoxicity plays a crucial role, however, the contribution of astrocytic activity in protecting neurons from excitotoxicity-induced damage is yet to be fully understood. In this work, we evaluated the effect of astrocytic activation by Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) on brain glucose metabolism in wild-type (WT) mice, and we investigated the effects of sustained astrocyte activation following an insult induced by intrahippocampal (iHPC) kainic acid (KA) injection using 2-deoxy-2-[18F]-fluoro-D-glucose (18F-FDG) positron emission tomography (PET) imaging, along with behavioral test, nuclear magnetic resonance (NMR) spectroscopy and histochemistry. Astrocytic Ca2+ activation increased the 18F-FDG uptake, but this effect was not found when the study was performed in knock out mice for type-2 inositol 1,4,5-trisphosphate receptor (Ip3r2-/-) nor in floxed mice to abolish glucose transporter 1 (GLUT1) expression in hippocampal astrocytes (GLUT1ΔGFAP). Sustained astrocyte activation after KA injection reversed the brain glucose hypometabolism, restored hippocampal function, prevented neuronal death, and increased hippocampal GABA levels. The findings of our study indicate that astrocytic GLUT1 function is crucial for regulating brain glucose metabolism. Astrocytic Ca2+ activation has been shown to promote adaptive changes that significantly contribute to mitigating the effects of KA-induced damage. This evidence suggests a protective role of activated astrocytes against KA-induced excitotoxicity.
PB Wiley
SN 0894-1491
YR 2024
FD 2024-08-26
LK https://hdl.handle.net/20.500.14352/110051
UL https://hdl.handle.net/20.500.14352/110051
LA eng
NO Hernández-Martín, N., Martínez, M. G., Bascuñana, P., Fernández de la Rosa, R., García-García, L., Gómez, F., Solas, M., Martín, E. D., & Pozo, M. A. (2024). Astrocytic Ca2+ activation by chemogenetics mitigates the effect of kainic acid-induced excitotoxicity on the hippocampus. Glia, 72(12), 2217–2230. https://doi.org/10. 1002/glia.24607
NO Ministerio de Ciencia, Innovación y Universidades (España)
DS Docta Complutense
RD 23 abr 2025